Carcinogenesis Advance Access published online on November 3, 2009
Carcinogenesis, doi:10.1093/carcin/bgp274
Senescence: an antiviral defense that is tumor suppressive?
Cancer Research Unit, Children's Medical Research Institute, 214 Hawkesbury Road, Westmead, New South Wales 2145, and Sydney Medical School, University of Sydney, New South Wales 2006 Australia
Correspondence: Roger Reddel, Children's Medical Research Institute, 214 Hawkesbury Road, Westmead, NSW 2145, Australia, email: rreddel{at}cmri.usyd.edu.au
Normal mammalian somatic cells proliferate a finite number of times in vitro before permanently withdrawing from the cell cycle into a cellular state referred to as senescence. Senescence may be triggered by excessive mitogenic stimulation or by various forms of cellular damage including excessive telomere shortening. Over the past decade, there has been continuing accumulation of evidence that senescence occurs in vivo, that it is relevant to aging, and that it has a tumor suppressor function. However, it has also become clear that the phenotype of senescence also has a number of puzzling features, including the secretion of pro-inflammatory factors that may foster tumorigenesis and also the senescence of neighboring cells. On the basis of these antagonistic pro- and anti-tumorigenic effects, and of the observation that many viruses have developed proteins that prevent senescence of the cells they infect, it is argued that the primary function of senescence may have been as an antiviral defense mechanism. Recent progress in understanding how tumor cells evade senescence is also reviewed here.
Key Words: Senescence • antiviral • Telomerase
Received October 30, 2009; revised October 30, 2009; accepted October 30, 2009.